II. Dosing: General pointers
- Sinemet (regular release) is by far the single most effective agent
- This agent should be the first line and main agent used for Parkinsonism
- All other agents are adjuncts only
- Dosing Threshold
- Identify the individual patient's optimal dose and use this dose at each dosing interval
- Using a lower dose below threshold will be inadequate
-
Food Interactions
- Take at least one hour before a meal or 2 hours after a meal
- Wearing off of effect
- See frequency of dosing of Sinemet below
- Most common cause of Insomnia
- May cause anxiety, nocturnal cramps
-
Dyskinesia (e.g. Choreiform movements)
- Dyskinesia is more age related than that of duration of Levodopa use
- Reducing each Levodopa dose decreases this adverse effect
- Amantadine decreases Dyskinesia
- Adverse Effects: Educate patients about serious effects (most are reduced by tapering dose)
- Drowsiness
- Pathologic Gambling, Hypersexuality, Excessive shopping/spending
- Hallucinations or Delusions
- Swelling
III. Preparations
- Carbidopa/Levodopa (Sinemet)
- Preferred option over sustained release
- Lower cost
- Better pharmacokinetics
- Less Drug Interactions
- Start at 25/100 orally three times daily
- Increase by one tablet every 1-2 days as needed
- Maximum : 3 tablets per dose
- Frequency of dose
- Initially give dose three times daily
- Long term, dose may wear off early
- Frequency may need to be increased to every 6 hours (at same number of tablets at each dose)
- Preferred option over sustained release
- Carbidopa/Levodopa Sustained release (Sinemet CR)
- Start at 50/200 PO bid
- Increase by one tablet every 3 days as needed
- Maximum : 8 tablets daily
- No benefit over immediate release in motor function
- Carbidopa/Levodopa fast onset, sustained release (Rytary)
- Onset within 1 hour, duration of 6 hours
- Costs 3-4 times more than generic Carbidopa/Levodopa
- May decrease "off time", the wearing off of activity between doses
- Consider in advanced Parkinsonism for "off time" problems despite four time daily dosing
- Typical Dose: 3-4 caps three times daily
- Requires higher dosing than other preparations due to lower bioavailability
- (2015) Presc Lett 22(7): 41
- Carbidopa/Levodopa/Entacapone (Stalevo)
- Start at 12.5/50/200 PO bid
- Increase slowly
- Maximum : 8 tablets daily
IV. References
- Ahlskog (2011) Mayo Internal Medicine Review Lecture
- Schim (2001) CMEA Medicine Lecture, San Diego
- Clarke (2003) Clin Evid 10:1582-98 [PubMed]
- Clarke (2004) Lancet Neurol 3:466-74 [PubMed]
- Gazewood (2013) Am Fam Physician 87(4): 267-73 [PubMed]
- Nutt (2005) N Engl J Med 353:1021-7 [PubMed]
- Olanow (2001) Neurology 56:S1-88 [PubMed]
- Rao (2006) Am Fam Physician 74:2046-56 [PubMed]
- Young (1999) Am Fam Physician 59(8):2155-67 [PubMed]
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| carbidopa-levodopa (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| CARBIDOPA-LEVODOPA 10-100 TAB | Generic | $0.15 each |
| CARBIDOPA-LEVODOPA 25-100 TAB | Generic | $0.10 each |
| CARBIDOPA-LEVODOPA 25-250 TAB | Generic | $0.18 each |
| CARBIDOPA-LEVODOPA-ENTA 100 MG | Generic | $1.90 each |
| CARBIDOPA-LEVODOPA-ENTA 125 MG | Generic | $1.82 each |
| CARBIDOPA-LEVODOPA-ENTA 150 MG | Generic | $1.59 each |
| CARBIDOPA-LEVODOPA-ENTA 200 MG | Generic | $2.25 each |
| CARBIDOPA-LEVODOPA-ENTA 50 MG | Generic | $1.93 each |
| CARBIDOPA-LEVODOPA-ENTA 75 MG | Generic | $1.85 each |
| sinemet (on 6/8/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| SINEMET 25-100 MG TABLET | Generic | $0.10 each |
| stalevo (on 1/4/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| STALEVO 100 TABLET | Generic | $1.90 each |
| STALEVO 150 TABLET | Generic | $1.59 each |
| STALEVO 200 TABLET | Generic | $2.25 each |
| rytary (on 3/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| RYTARY ER 23.75 MG-95 MG CAP | $2.47 each | |
| RYTARY ER 36.25 MG-145 MG CAP | $2.48 each | |
| RYTARY ER 48.75 MG-195 MG CAP | $2.47 each | |
| RYTARY ER 61.25 MG-245 MG CAP | $3.12 each | |
Ontology: Levodopa (C0023570)
| Definition (NCI) | An amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS. |
| Definition (MSH) | The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. |
| Definition (CSP) | naturally occuring form of DOPA and precursor of dopamine; used as an antiparkinsonian agent; unlike dopamine it can be administered orally. |
| Definition (PDQ) | An amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42622&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42622&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C611" NCI Thesaurus) |
| Concepts | Pharmacologic Substance (T121) , Neuroreactive Substance or Biogenic Amine (T124) , Amino Acid, Peptide, or Protein (T116) |
| MSH | D007980 |
| SnomedCT | 15383004, 387086006, 65955006 |
| LNC | LP32555-2, LP16328-4, MTHU015998 |
| English | L-3,4-Dihydroxyphenylalanine, L-Dopa, Levodopa, 3 Hydroxy L tyrosine, 3-Hydroxy-L-tyrosine, L 3,4 Dihydroxyphenylalanine, (--)-3-(3,4-Dihydroxyphenyl)-L-alanine, beta-(3,4-Dihydroxyphenyl)-L-alanine, (--)-2Amino-3-)3,4-dihydroxyphenyl)propanoic Acid, DOPA A L, levodopa, LEVODOPA, Levodopa [Chemical/Ingredient], l-dopa, l dopa levodopa, dopa l, l dopa, L 3,4-dihydroxyphenylalanine, (--)-2Amino-3-(3,4-dihydroxyphenyl)propanoic Acid, L-DOPA, .beta.-(3,4-Dihydroxyphenyl)-L-alanine, L-.beta.-(3,4-Dihydroxyphenyl)alanine, (-)-3-(3,4-Dihydroxyphenyl)-L-alanine, L(-)-Dopa, 3-(3,4-Dihydroxyphenyl)-L-alanine, L-dopa, L-3-hydroxytyrosine, L-Dopa - Levodopa, L-dopa preparation, Levodopa (product), Levodopa (substance), L Dopa |
| Swedish | Levodopa |
| Czech | levodopa |
| Spanish | L-dopa, L-3-hidroxitirosina, levo-dopa, levodopa (producto), levodopa (sustancia), levodopa, preparado de L-dopa, L-Dopa, Levodopa |
| Finnish | Levodopa |
| Russian | LEVODOFA, LEVODOPA, L-DOFA, L-DOPA, L-ДОФА, ЛЕВОДОПА, ЛЕВОДОФА |
| French | 3-Hydroxy-L-tyrosine, L-Dopa, Lévodopa |
| German | DOPA A L, L-Dopa, Levodopa |
| Croatian | LEVODOPA |
| Polish | Lewodopa, L-dopa |
| Japanese | L-ジオキシフェニルアラニン, L-ドーパ, ドパストン, ドパール, レボドパ, レボドーパ, Lド-パ, Lドパ |
| Italian | Levodopa |
| Portuguese | L-Dopa, Levodopa |
Ontology: Sinemet (C0074559)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | C009265 |
| English | Sinemet, BMS brand of carbidopa, levodopa drug combination, sinemet |
Ontology: Carbidopa / Levodopa (C0353697)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| SnomedCT | 323113004, 372605005, 346377002, 404830004 |
| English | Levodopa with carbidopa, CARBIDOPA/LEVODOPA, carbidopa + levodopa, carbidopa + levodopa (medication), Carbidopa-Levodopa, carbidopa-levodopa, Carbidopa / Levodopa, levodopa carbidopa, carbidopa levodopa, co careldopa, co-careldopa, levodopa with carbidopa, Levodopa with carbidopa (product), Co-careldopa (substance), Co-careldopa (product), Carbidopa+levodopa (product), Carbidopa+levodopa, Levodopa with carbidopa (substance), Carbidopa and Levodopa, Co-careldopa |
| Spanish | levodopa con carbidopa, co-careldopa (producto), levodopa-carbidopa, levodopa-carbidopa (sustancia), levodopa con carbidopa (producto), co-careldopa, co-careldopa (sustancia), carbidopa + levodopa (producto), carbidopa + levodopa |
Ontology: Carbidopa / entacapone / Levodopa (C1329991)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| SnomedCT | 410860008 |
| English | CARBIDOPA/LEVODOPA/ENTACAPONE @ @ UNIDENTIFIED, CARBIDOPA/LEVODOPA/ENTACAPONE UNIDENTIFIED, CARBIDOPA/ENTACAPONE/LEVODOPA, carbidopa + levodopa + entacapone, carbidopa + levodopa + entacapone (medication), Carbidopa / entacapone / Levodopa, Carbidopa/Entacapone/Levodopa, carbidopa/entacapone/levodopa, Carbidopa+levodopa+entacapone (product), Carbidopa+levodopa+entacapone, Levodopa+careldopa+entacapone |
| Spanish | carbidopa+levodopa+entacapona (producto), carbidopa+levodopa+entacapona |
